The objectives of this research are: 1) to conclusively demonstrate that the extractable nuclear antigen (ENA) protects New Zealand White/New Zealand Black F1 mice (NZB/NZW) from the naturally occurring nephritis common to these animals. 2) To correlate the serological, pathological, immunopathological and functional changes in order to define potential mechanisms of protection. 3) To determine by in vitro tests if ENA alters the size or reactivity of DNA-anti DNA complexes. 4) To determine if ENA protection is associated with general immunosuppression in NZB/NZW and other strains of mice. 5) To purify ENA, quantitate the RNA, DNA, protein, and lipid present, separate the Sm nuclear antigen component from the RNP component of NEA, and determine the RNA specificity of ENA. 6) To test the purified reagents for protective activity and in vitro or in vivo effect on immune phenomena. 7) To determine the presence of spontaneous occurring anti-ENA in NZB, NZW, and NZB/NZW mice. 8) To immunize NZB/NZW mice with ENA and determine the effect of antibody to ENA on the nephritis. Methods for studying the effects of ENA on the nephritis of mice include determining antibody to DNA and RNA by radioactive binding and to DNA by hemagglutination, antinuclear antibodies by indirect fluorescence, quantitative grading of histologic injury, occurrence and pattern of gamma globulin and complement deposits in the kidneys, and tests of renal function. Antibody activity will be tested with ENA added to test the influence of ENA on DNA-anti DNA reactions and sizes of the resulting complexes will be compared. Standard techniques for separation of molecules, our immunological reagents, and radioactive cellular RNA classes will be used to purify ENA, and define the RNA specificity of ENA. The presence of spontaneous antibody to ENA will be determined in NZ mice and antibody to ENA will be induced by immunization to determine the effect of ENA antibody on NZB/NZW nephritis.